The goal of this project is to characterize interactions between B lymphocyte subpopulations which regulate responses of these cells. Previous work from this laboratory showed that a B lymphocyte hybridoma (2.4G2) produced a low molecular weight substance(s) which triggered B lymphocytes to both proliferate and secrete antibody. This result suggested that certain B lymphocytes might regulate the response of other B cells. Our current studies have shown that large "activated" B lymphocytes obtained directly from mice or B lymphoblasts induced in vitro with F(ab')2 anti-mu significantly augment the responses of small "resting" B lymphocytes to F(ab')2 and lymphokines. Proliferation was augmented 2-4 fold while antibody production was augmented 4-5 fold. This effect was specific for "activated" B lymphocytes in that other cell types did not have this effect. Kinetic experiments revealed that the augmenting signal was effective after stimulation via antigen receptors but prior to the effects of lymphokines. The augmenting effect does not appear to be genetically restricted. Investigation of the nature of the signal revealed that neither supernatants nor plasma membranes from activated B cells alone augmented responses but both together did. These studies suggest that interactions between B lymphocytes are important in regulating humoral immune responses.